Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen
Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (A...
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description | Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes. |
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In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0117778</identifier><identifier>PMID: 25679777</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviruses ; Animals ; Antibodies, Monoclonal - genetics ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - metabolism ; Antibody Formation ; Antigenic determinants ; Antigens ; Antigens, Protozoan - chemistry ; Antigens, Protozoan - genetics ; Antigens, Protozoan - immunology ; Breast cancer ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell activation ; Cell proliferation ; Chagas Disease - immunology ; Chagas Disease - metabolism ; Cloning ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Epitopes ; Epitopes, T-Lymphocyte - immunology ; Female ; Genes ; HEK293 Cells ; Humans ; Immune response ; Immune system ; Immunization ; Immunodominance ; Immunodominant Epitopes - immunology ; Infections ; Information technology services ; Interferon ; Laboratories ; Leishmania major ; Lymphocytes ; Lymphocytes T ; Mice ; Monoclonal antibodies ; Neuraminidase - genetics ; Neuraminidase - immunology ; Parasitology ; Peptides - immunology ; Poly (I:C) ; Polyinosinic:polycytidylic acid ; Protein Binding - immunology ; Proteins ; Protozoa ; Receptors ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Recombinant Fusion Proteins - metabolism ; Science ; T cell receptors ; T cells ; Trypanosoma cruzi ; Trypanosoma cruzi - immunology ; Vaccines ; Yersinia pestis ; γ-Interferon</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0117778-e0117778</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Rampazo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Rampazo et al 2015 Rampazo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e0a47f58c83ef954aba914a8aab9d1afc5b025e7f3fb6c223eb63e8db6ff5c653</citedby><cites>FETCH-LOGICAL-c692t-e0a47f58c83ef954aba914a8aab9d1afc5b025e7f3fb6c223eb63e8db6ff5c653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332658/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332658/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25679777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rampazo, Eline V</creatorcontrib><creatorcontrib>Amorim, Kelly N S</creatorcontrib><creatorcontrib>Yamamoto, Marcio M</creatorcontrib><creatorcontrib>Panatieri, Raquel Hoffmann</creatorcontrib><creatorcontrib>Rodrigues, Mauricio M</creatorcontrib><creatorcontrib>Boscardin, Silvia B</creatorcontrib><title>Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. 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genetics</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Antibody Formation</topic><topic>Antigenic determinants</topic><topic>Antigens</topic><topic>Antigens, Protozoan - chemistry</topic><topic>Antigens, Protozoan - genetics</topic><topic>Antigens, Protozoan - immunology</topic><topic>Breast cancer</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell activation</topic><topic>Cell proliferation</topic><topic>Chagas Disease - immunology</topic><topic>Chagas Disease - metabolism</topic><topic>Cloning</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Female</topic><topic>Genes</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunization</topic><topic>Immunodominance</topic><topic>Immunodominant Epitopes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rampazo, Eline V</au><au>Amorim, Kelly N S</au><au>Yamamoto, Marcio M</au><au>Panatieri, Raquel Hoffmann</au><au>Rodrigues, Mauricio M</au><au>Boscardin, Silvia B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-13</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117778</spage><epage>e0117778</epage><pages>e0117778-e0117778</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25679777</pmid><doi>10.1371/journal.pone.0117778</doi><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1656698838 |
source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Adenoviruses Animals Antibodies, Monoclonal - genetics Antibodies, Monoclonal - immunology Antibodies, Monoclonal - metabolism Antibody Formation Antigenic determinants Antigens Antigens, Protozoan - chemistry Antigens, Protozoan - genetics Antigens, Protozoan - immunology Breast cancer CD4 antigen CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell activation Cell proliferation Chagas Disease - immunology Chagas Disease - metabolism Cloning Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Deoxyribonucleic acid Disease Models, Animal DNA Epitopes Epitopes, T-Lymphocyte - immunology Female Genes HEK293 Cells Humans Immune response Immune system Immunization Immunodominance Immunodominant Epitopes - immunology Infections Information technology services Interferon Laboratories Leishmania major Lymphocytes Lymphocytes T Mice Monoclonal antibodies Neuraminidase - genetics Neuraminidase - immunology Parasitology Peptides - immunology Poly (I:C) Polyinosinic:polycytidylic acid Protein Binding - immunology Proteins Protozoa Receptors Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - metabolism Science T cell receptors T cells Trypanosoma cruzi Trypanosoma cruzi - immunology Vaccines Yersinia pestis γ-Interferon |
title | Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen |
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